1. Field of the Invention
The present invention relates generally to the field of β-cell physiology and more specifically to the identification of agents that modulate insulin expression and production.
2. Background Information
Diabetes mellitus is a familiar disease well known to lead to morbidity and mortality. Diabetes is characterized by high blood glucose levels, which result from defects in insulin production, insulin action, or both. Both genetics and environmental factors, such as obesity and lack of exercise, are known factors contributing to pathology of the disease.
There are two primary types of diabetes, Types I and II. Type I, or insulin-dependent diabetes mellitus (IDDM) or juvenile-onset diabetes is due to autoimmune destruction of insulin-producing β-cells in the pancreatic islets. Type I usually occurs in childhood or young adults. However the disease may occur at any age. Treatments options typically include daily injections of insulin, combined with frequent testing of blood glucose levels to guide adjustment of insulin doses.
Type II, or noninsulin-dependent diabetes mellitus (NDDM) or adult-onset diabetes typically develops in adulthood and is characterized as a metabolic disorder resulting from the body's inability to make enough, or properly use, insulin. NDDM is associated with resistance of glucose-utilizing tissues like adipose tissue, muscle, and liver, to the actions of insulin. Type II diabetes usually begins as insulin resistance, a disorder in which the cells do not use insulin properly, and as the need for insulin rises, the pancreas gradually loses its ability to produce insulin. Type 2 diabetes is the most common form of the disease accounting for 90-95 percent of diabetes.
A third type of diabetes is known as gestational diabetes. This disease is linked to glucose intolerance as diagnosed in pregnant women.
Other disorders associated with diabetes include hyperinsulinemia, which refers to the overproduction of insulin by pancreatic cells. Hyperinsulinemia usually results from insulin resistance, a condition characterized by cellular resistance to the action of insulin. Insulin resistance, is characterized when a normal amount of insulin produces a subnormal biologic (metabolic) response. Additionally, lipotoxemia is a process characterized by the accumulation of excess fatty acids accompanied by triglyceride in parenchymal cells of multiple tissues including skeletal and cardiac myocytes, hepatocytes, and pancreatic beta cells resulting in chronic cellular dysfunction and injury.
The insulin promoter is the target of diabetogenic molecules, such as fatty acids, which play a role in the onset and characterization of diabetes. As such, innovative screening methods are needed to identify new agents that may be useful for the treatment and prevention of diabetes and related disorders.